Abstract
Living organisms repeatedly encounter stressful events and apply various strategies to survive. Polyamines are omnipresent bioactive molecules with multiple functions. Their transient synthesis, inducible by numerous stressful stimuli, is termed the polyamine stress response. Animals developed evolutionarily conserved strategies to cope with stresses. The urea cycle is an ancient attribute that deals with ammonia excess in terrestrial species. Remarkably, most fish retain the urea cycle genes fully expressed during the early stages of development and silenced in adult animals. Environmental challenges instigate urea synthesis in fish despite substantial energetic costs, which poses the question of the urea cycle's evolutionary significance. Arginase plays a critical role in oxidative stress-dependent reactions being the final urea cycle enzyme. Its unique subcellular localization, high inducibility, and several regulation levels provide a supreme ability to control the polyamine synthesis rate. Notably, oxidative stress instigates the arginase-1 activity in mammals. Arginase is also dysregulated in aging organisms' brain and muscle tissues, indicating its role in the pathogenesis of age-associated diseases. We designed a study to investigate the levels of the urea cycle and polyamine synthesis-related enzymes in a fish model of acute hypoxia. We evidence synchronized elevation of arginase-2 and ornithine decarboxylase following oxidative stress in adult fish and aging animals signifying the specific function of arginase-2 in fish. Moreover, we demonstrate oxidative stress-associated polyamine synthesis' induction and urea cycle' arrest in adult fish. The subcellular arginase localization found in the fish seems to correspond to its possible evolutionary roles.
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Abbreviations
- CAT:
-
Catalase
- CNS:
-
Central nervous system
- CPS:
-
Carbamoyl phosphate synthetase
- DOL:
-
Dissolved oxygen level
- GPX:
-
Glutathione peroxidase
- HIF-1:
-
Hypoxia-inducible factor 1
- IHC:
-
Immunohistochemical staining
- ODS:
-
Ornithine decarboxylase
- OTC:
-
Ornithine transcarbamylase
- PSR:
-
Polyamine stress response
- ROS:
-
Reactive oxygen species
- SOD:
-
Superoxide dismutase
- TNFα:
-
Tumor necrosis factor-alpha
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DK conceived and supervised the study and edited the manuscript. BP designed the study, performed the image acquisition and analysis, and wrote the manuscript. BB, IK, IBZ performed experiments, analyzed the results, and revised the manuscript. All authors read and approved the final version of the manuscript.
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18_2021_4043_MOESM1_ESM.tif
Fig. S1. The urea cycle diagram in fish (enzymes, products, and steps). The urea cycle converts toxic ammonia to urea, which bears two amino groups in its structure, one derived from ammonia and another from aspartate. The enzymes: carbamoyl phosphate synthetase 3 (CPS3), ornithine transcarbamylase (Otc), argininosuccinate synthetase (Ass), argininosuccinate lyase (Asl), arginase (Arg), ornithine decarboxylase (Odc)
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Banerjee, B., Khrystoforova, I., Polis, B. et al. Acute hypoxia elevates arginase 2 and induces polyamine stress response in zebrafish via evolutionarily conserved mechanism. Cell. Mol. Life Sci. 79, 41 (2022). https://doi.org/10.1007/s00018-021-04043-x
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DOI: https://doi.org/10.1007/s00018-021-04043-x